First hESC Trial Kaput

The world’s first clinical trial testing a human embryonic stem cell (hESC) therapy is closing to further enrollment after a long, rocky ride, according to the Geron Corporation. The company, which started the trial two years ago, announced the trial’s shuttering Monday (November 14), along with its decision to withdraw from the stem cell sector altogether—not for lack of promise, but simply a strategic move to stay afloat during hard economic times.

“It’s certainly going to have a very chilling effect,” said Robert Lanza, chief scientific officer at Advanced Cell Technology, the only other company currently engaged in clinical trials involving hESCs. “There’s a lot of exciting potential here in this field, and it would just be a real shame for this not to move ahead full steam.”

“It was a bit sad” to hear that Geron is cancelling its stem cell trial, agreed Bob Palay, CEO of stem cell manufacturer Cellular Dynamics International. “But it doesn’t say anything about the science. ... I think you’ll see in the coming years many, many new trials.”

Geron first filed its 21,000-page application for the Phase I trial in March 2008, and finally received approval from the US Food and Drug Administration in January 2009. The experimental therapy involved the injection of hESC-derived progenitors of neural support tissue into the spinal cord of patients with severe spinal cord injury. But then in August 2009, before any patients could receive the therapy, the FDA put a hold on the trial after continued animal experiments turned up a possible side effect of the treatment—microscopic cysts. The cysts appeared in low frequency, and did not appear to proliferate or cause any adverse effects on the animals, and in July 2010, the company announced the trial was back on track, after an additional preclinical animal study.

So far, four patients have been treated with the one-time injection of a low dose of cells as part of this initial safety trial. All four patients , who will continue to be monitored by Geron, have tolerated the treatments well and not shown any signs of adverse effects, according to the company, but so far, no patients have shown any neurologic changes that are consistent with efficacy. Patients who had already received approval to join the trial will still receive treatment, Stephen Kelsey, executive vice president and head of research & development, added at a press conference held today (November 15). Kelsey couldn’t say how many patients were in this position, but the company had originally aimed to enroll a total of eight patients in the trial.

“Deciding to move out of the stem cell business was a very difficult decision to make,” Geron CEO John Scarlett said at the press conference. “We’re making these changes because in the current environment of scarcity and uncertain economic conditions, we need to focus our resources on...our cancer programs,” which are expected to generate results as soon as next year. Stem cell trial results, Scarlett added, weren’t expected until 2014. “[It] was a business decision,” he said.

“Of course it would be best if this trial had gone forward,” Palay noted, “but as far as the future of the stem cell field...you should think of this as a very temporary setback.”

Indeed, there are still two ongoing hESC trials, both being conducted by Advanced Cell Technology, for two forms of genetic eye diseases—Stargardt's macular dystrophy and dry age-related macular degeneration. The results have not been made public yet, but “we’ve collected a great deal of data,” Lanza said, and “we couldn’t be more pleased with the results. ... I think it’s an exciting indication, and there’s every reason to be hopeful.”

And there will likely be more stem cells trials on the way, Konrad Hochedlinger of Harvard Medical School and Massachusetts General Hospital wrote in an email to The Scientist. “I think that others will pick up where Geron left off, but it may take a while for others to catch up.”

One thing working in the field’s favor is the fact that Geron helped pave the regulatory way for other stem cell therapies, said Sheng Ding, a stem cell biologist at the Gladstone Institutes and the University of California, San Francisco. “Geron's past efforts had cleared out a FDA path for pluripotent stem cells,” he wrote in an email to The Scientist. “With now more advanced and much better technologies to modify stem cells with much greater efficacy, some of the new stem cell products will succeed.”

Geron’s decision to terminate the trial also means that the company is eliminating 66 full-time positions—38 percent of its workforce. The company is actively seeking investors interested in acquiring the stem cell portion of its business.

For now, Geron will be focusing its efforts on its oncology programs. In particular, the company is currently testing its telomerase inhibitor, called Imetelstat, in several Phase II studies, including one for metastatic breast cancer and one for advanced non-small cell lung cancer. Geron’s LRP-directed peptide-drug conjugate program, which aims to use molecules to deliver anti-cancer drugs to brain tumors, also has a candidate entering two Phase II trials for brain metastases arising from non-small cell lung cancer and breast cancer.

“Both clinical stage molecules emerging from these programs are unique in their class and both currently represent the only molecules within their respective class to enter clinical trials,” Kelsey said. “Both programs address areas of large unmet medical need and have the potential to produce significant clinical impact on patient outcomes across a range of malignancies.”

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@StemCellBlogger:disqus hESCs have only been around for 13 years compared to adult stem cells 30+ years.... give it some time... human embryonic stem cells (especially ACT's embryo SAFE blastomere-derived) will be THE GOLD standard :)Â watch and SEEE the difference...soon..

michaelbrom- Not even close. Â Â Embryonic stem cellshave been around for way longer than since James Thompson and friends derivedthe first human embryonic stem cell line at the University of Wisconsin-Madisonin 1998.

Â

Toclarify:

Researchin the human stem cell field grew out of findings by Canadian scientists ErnestA. McCulloch and James E. Till in the 1960s.

Blastomeresisolated from the ICM of mammalian embryos and grown in culture are known asembryonic stem (ES) cells. These pluripotent cells, when grown in a carefullycoordinated media, can give rise to all three germ layers (ectoderm, endoderm,and mesoderm) of the adult body.

And then we get to what you consider the â€œdiscoveryof embryonic stem cellsâ€쳌:Â

1998 - James Thomson and coworkers derive the first humanembryonic stem cell line at the University of Wisconsin-Madison.

Â

Notto worry, though.Â Adult stem cells HAVE beenused in bone marrow transplants for over 40 years so they still have the upper handin â€œtime weâ€™ve worked with them.â€쳌Â Then again,it was only in 1998 that adult stem cells were considered for treating other illnesses.

Â

Justout of curiosity, how do you plan on addressing these embryonic stem cell issuesto name a few?

They create cysts and tumors thatcan develop into cancer at the site of the injection and injury, rejection issuesrequire immunosuppressive drugs for the ill patient, embryonic stem cells (andinduced pluripotent stem cells) carry the genetic anomalies of the donor, as mentioned before "100% fruitless (in regard to generating treatments) for well-funded and government supported scientists around the world for the last 13 years," theyhave to date treated zero diseases successfully, scientists probably need tocure cancer first to use them.

Â

But if you can come up with a way to match the success rate of adult stem cell treatments (~65% of patients have significant improvement in their incurable, chronic or terminal illnesses) and do so without the side effects alluded to above (adult stem cells have virtually zero side effects except for sometimes additionally fixing more than the intended organ/illness) then I would love to hear about it!

â€œDeciding to move out of the stem cell business was a very difficult decision to make,â€쳌 Geron CEO John Scarlett said at the press conference. â€œWeâ€™re making these changes because in the current environment of scarcity and uncertain economic conditions, we need to focus our resources onâ€¦our cancer programs,â€쳌 which are expected to generate results as soon as next year. Stem cell trial results, Scarlett added, werenâ€™t expected until 2014. â€œ[It] was a business decision.â€쳌

Clearly, this is not a failure of human embryonic stem cells as a mode of clinical translational therapy, but rather a stark comment on the economy. Many biotechnology and pharmaceutical firms are feeling the crunch of this economy, and choose to change a path to one that preserves capitol and jobs.

Elsewhere in the article it is pointed out that Geron was the first to plow the path in the FDA promoting future trials using human embryonic stem cells. I see this as one major milestone completed.

The next item concernsÂ the type of spinal injury in question. I am assuming that this was not a totally severed spinal cord. If so, it would be a remarkable "proof of concept" that,Â human embryonic stems cells are indeed cells that promote miraculous recoveryÂ not unlikeÂ Dr. Erlich's "magic bullet" curing syphilis. Even a minor compression of the spinal cordÂ along theÂ cervical vertebrae can render a person unable to walk, or lift their arms.Â Release of theÂ area of compression alongÂ this portion of the spinal cordÂ using cervical laminectomy withÂ fusion and physical therapy,Â canÂ take up to two or more years for the individual to regain the ability to walk or regain normal use of arms or hands. What are the time constraints in the Geron study?

I cant believe that they filed a 21,000 page application with the FDA. What FDA clerk is going to read 21,000 pages? Perhaps I am unfamiliar with the FDA procedures, but there is something about this that strikes me as absurd.

I looks to me like the costs of complying with government-created obstacles have now overwhelmed this medical field, in the U.S. at least. Hopefully the situation will be better elsewhere -- perhaps Asia will take the reins and before long we'll all be going there for medical treatments.

If stem cell treatments were a boxing match, Embryonic stem cell treatments would be the 500 lb Gorilla and Adult stem cell treatments would be the small, unknown underdog. Today, the Gorilla threw in the towel!

What would cause the leading Embryonic stem cell Pharmaceutical company with multiple Embryonic stem cell products in development to end all of their Embryonic stem cell programs? What does it mean for patients who were waiting with desperate hope for the benefits of Embryonic stem cells? http://repairstemcell.wordpres...

@rusty, embryonic research has been 100% fruitless (in regard to generating treatments) for well-funded and government supported scientists around the world for the last 13 years.Â Embryonic stem cells are the only significant obstacles to embryonic stem cell treatments.Â Adult stem cells on the other hand have successfully treated 10s of thousands over the past decade.

@StemCellBlogger:disqus hESCs have only been around for 13 years compared to adult stem cells 30+ years.... give it some time... human embryonic stem cells (especially ACT's embryo SAFE blastomere-derived) will be THE GOLD standard :)Â watch and SEEE the difference...soon..

michaelbrom- Not even close. Â Â Embryonic stem cellshave been around for way longer than since James Thompson and friends derivedthe first human embryonic stem cell line at the University of Wisconsin-Madisonin 1998.

Â

Toclarify:

Researchin the human stem cell field grew out of findings by Canadian scientists ErnestA. McCulloch and James E. Till in the 1960s.

Blastomeresisolated from the ICM of mammalian embryos and grown in culture are known asembryonic stem (ES) cells. These pluripotent cells, when grown in a carefullycoordinated media, can give rise to all three germ layers (ectoderm, endoderm,and mesoderm) of the adult body.

And then we get to what you consider the â€œdiscoveryof embryonic stem cellsâ€쳌:Â

1998 - James Thomson and coworkers derive the first humanembryonic stem cell line at the University of Wisconsin-Madison.

Â

Notto worry, though.Â Adult stem cells HAVE beenused in bone marrow transplants for over 40 years so they still have the upper handin â€œtime weâ€™ve worked with them.â€쳌Â Then again,it was only in 1998 that adult stem cells were considered for treating other illnesses.

Â

Justout of curiosity, how do you plan on addressing these embryonic stem cell issuesto name a few?

They create cysts and tumors thatcan develop into cancer at the site of the injection and injury, rejection issuesrequire immunosuppressive drugs for the ill patient, embryonic stem cells (andinduced pluripotent stem cells) carry the genetic anomalies of the donor, as mentioned before "100% fruitless (in regard to generating treatments) for well-funded and government supported scientists around the world for the last 13 years," theyhave to date treated zero diseases successfully, scientists probably need tocure cancer first to use them.

Â

But if you can come up with a way to match the success rate of adult stem cell treatments (~65% of patients have significant improvement in their incurable, chronic or terminal illnesses) and do so without the side effects alluded to above (adult stem cells have virtually zero side effects except for sometimes additionally fixing more than the intended organ/illness) then I would love to hear about it!

â€œDeciding to move out of the stem cell business was a very difficult decision to make,â€쳌 Geron CEO John Scarlett said at the press conference. â€œWeâ€™re making these changes because in the current environment of scarcity and uncertain economic conditions, we need to focus our resources onâ€¦our cancer programs,â€쳌 which are expected to generate results as soon as next year. Stem cell trial results, Scarlett added, werenâ€™t expected until 2014. â€œ[It] was a business decision.â€쳌

Clearly, this is not a failure of human embryonic stem cells as a mode of clinical translational therapy, but rather a stark comment on the economy. Many biotechnology and pharmaceutical firms are feeling the crunch of this economy, and choose to change a path to one that preserves capitol and jobs.

Elsewhere in the article it is pointed out that Geron was the first to plow the path in the FDA promoting future trials using human embryonic stem cells. I see this as one major milestone completed.

The next item concernsÂ the type of spinal injury in question. I am assuming that this was not a totally severed spinal cord. If so, it would be a remarkable "proof of concept" that,Â human embryonic stems cells are indeed cells that promote miraculous recoveryÂ not unlikeÂ Dr. Erlich's "magic bullet" curing syphilis. Even a minor compression of the spinal cordÂ along theÂ cervical vertebrae can render a person unable to walk, or lift their arms.Â Release of theÂ area of compression alongÂ this portion of the spinal cordÂ using cervical laminectomy withÂ fusion and physical therapy,Â canÂ take up to two or more years for the individual to regain the ability to walk or regain normal use of arms or hands. What are the time constraints in the Geron study?

I cant believe that they filed a 21,000 page application with the FDA. What FDA clerk is going to read 21,000 pages? Perhaps I am unfamiliar with the FDA procedures, but there is something about this that strikes me as absurd.

I looks to me like the costs of complying with government-created obstacles have now overwhelmed this medical field, in the U.S. at least. Hopefully the situation will be better elsewhere -- perhaps Asia will take the reins and before long we'll all be going there for medical treatments.

If stem cell treatments were a boxing match, Embryonic stem cell treatments would be the 500 lb Gorilla and Adult stem cell treatments would be the small, unknown underdog. Today, the Gorilla threw in the towel!

What would cause the leading Embryonic stem cell Pharmaceutical company with multiple Embryonic stem cell products in development to end all of their Embryonic stem cell programs? What does it mean for patients who were waiting with desperate hope for the benefits of Embryonic stem cells? http://repairstemcell.wordpres...

@rusty, embryonic research has been 100% fruitless (in regard to generating treatments) for well-funded and government supported scientists around the world for the last 13 years.Â Embryonic stem cells are the only significant obstacles to embryonic stem cell treatments.Â Adult stem cells on the other hand have successfully treated 10s of thousands over the past decade.

I looks to me like the costs of complying with government-created obstacles have now overwhelmed this medical field, in the U.S. at least. Hopefully the situation will be better elsewhere -- perhaps Asia will take the reins and before long we'll all be going there for medical treatments.

If stem cell treatments were a boxing match, Embryonic stem cell treatments would be the 500 lb Gorilla and Adult stem cell treatments would be the small, unknown underdog. Today, the Gorilla threw in the towel!

What would cause the leading Embryonic stem cell Pharmaceutical company with multiple Embryonic stem cell products in development to end all of their Embryonic stem cell programs? What does it mean for patients who were waiting with desperate hope for the benefits of Embryonic stem cells? http://repairstemcell.wordpres...

@rusty, embryonic research has been 100% fruitless (in regard to generating treatments) for well-funded and government supported scientists around the world for the last 13 years.Â Embryonic stem cells are the only significant obstacles to embryonic stem cell treatments.Â Adult stem cells on the other hand have successfully treated 10s of thousands over the past decade.

@StemCellBlogger:disqus hESCs have only been around for 13 years compared to adult stem cells 30+ years.... give it some time... human embryonic stem cells (especially ACT's embryo SAFE blastomere-derived) will be THE GOLD standard :)Â watch and SEEE the difference...soon..

michaelbrom- Not even close. Â Â Embryonic stem cellshave been around for way longer than since James Thompson and friends derivedthe first human embryonic stem cell line at the University of Wisconsin-Madisonin 1998.

Â

Toclarify:

Researchin the human stem cell field grew out of findings by Canadian scientists ErnestA. McCulloch and James E. Till in the 1960s.

Blastomeresisolated from the ICM of mammalian embryos and grown in culture are known asembryonic stem (ES) cells. These pluripotent cells, when grown in a carefullycoordinated media, can give rise to all three germ layers (ectoderm, endoderm,and mesoderm) of the adult body.

And then we get to what you consider the â€œdiscoveryof embryonic stem cellsâ€쳌:Â

1998 - James Thomson and coworkers derive the first humanembryonic stem cell line at the University of Wisconsin-Madison.

Â

Notto worry, though.Â Adult stem cells HAVE beenused in bone marrow transplants for over 40 years so they still have the upper handin â€œtime weâ€™ve worked with them.â€쳌Â Then again,it was only in 1998 that adult stem cells were considered for treating other illnesses.

Â

Justout of curiosity, how do you plan on addressing these embryonic stem cell issuesto name a few?

They create cysts and tumors thatcan develop into cancer at the site of the injection and injury, rejection issuesrequire immunosuppressive drugs for the ill patient, embryonic stem cells (andinduced pluripotent stem cells) carry the genetic anomalies of the donor, as mentioned before "100% fruitless (in regard to generating treatments) for well-funded and government supported scientists around the world for the last 13 years," theyhave to date treated zero diseases successfully, scientists probably need tocure cancer first to use them.

Â

But if you can come up with a way to match the success rate of adult stem cell treatments (~65% of patients have significant improvement in their incurable, chronic or terminal illnesses) and do so without the side effects alluded to above (adult stem cells have virtually zero side effects except for sometimes additionally fixing more than the intended organ/illness) then I would love to hear about it!

â€œDeciding to move out of the stem cell business was a very difficult decision to make,â€쳌 Geron CEO John Scarlett said at the press conference. â€œWeâ€™re making these changes because in the current environment of scarcity and uncertain economic conditions, we need to focus our resources onâ€¦our cancer programs,â€쳌 which are expected to generate results as soon as next year. Stem cell trial results, Scarlett added, werenâ€™t expected until 2014. â€œ[It] was a business decision.â€쳌

Clearly, this is not a failure of human embryonic stem cells as a mode of clinical translational therapy, but rather a stark comment on the economy. Many biotechnology and pharmaceutical firms are feeling the crunch of this economy, and choose to change a path to one that preserves capitol and jobs.

Elsewhere in the article it is pointed out that Geron was the first to plow the path in the FDA promoting future trials using human embryonic stem cells. I see this as one major milestone completed.

The next item concernsÂ the type of spinal injury in question. I am assuming that this was not a totally severed spinal cord. If so, it would be a remarkable "proof of concept" that,Â human embryonic stems cells are indeed cells that promote miraculous recoveryÂ not unlikeÂ Dr. Erlich's "magic bullet" curing syphilis. Even a minor compression of the spinal cordÂ along theÂ cervical vertebrae can render a person unable to walk, or lift their arms.Â Release of theÂ area of compression alongÂ this portion of the spinal cordÂ using cervical laminectomy withÂ fusion and physical therapy,Â canÂ take up to two or more years for the individual to regain the ability to walk or regain normal use of arms or hands. What are the time constraints in the Geron study?

I cant believe that they filed a 21,000 page application with the FDA. What FDA clerk is going to read 21,000 pages? Perhaps I am unfamiliar with the FDA procedures, but there is something about this that strikes me as absurd.

If you read up about the other company conducting a human embryonic stem cell trial (Advanced Cell Tech) they are using terminally differentiated RPE cells derived from an embryonic stem cell line. They also have an extremely effective assay test that can identify any undifferentiated stem cells before they are injected. This should make any formation of teratomas Â nil. Regarding immunosuppression, they have minimized the need for this by operating in an immune privileged site (the eye). To deal with the moral issue, the company has a method of producing stem cells that does Â not destroy the embryo( single cell blastomere method)

To follow up on natboling1 comments, cell soting can be used to separate potentially harmful cells from hESCs. This can be acheived through labeling with a specific biomarker.

Commenting on the morass of citations that StemCellBlogger has previously listed, touting adult stem cells as the way to salvation, even with donor human hematopoietic stem cellsÂ (hHESCs) (adult stem cells), usedÂ in the treatment of leukemia patients,Â a patientÂ must undergo aÂ radiation treatment toÂ suppressÂ their immuneÂ systemÂ prior to receiving the donorÂ hHESCs. StemCellBlogger commented on the need for immunosuppression when using hESCs inÂ clinical translational therapy. Given that a patient must receive a near lethal dose of radiation, knocking out their immune systemÂ BEFORE receiving hHESCs from aÂ registered DONOR, flies in the face of reason when compared to the immunosuppression required for hESC infusion.Â A patient receivng either a liver, kidney, pancreas or dual kidney pancreas organ transplant receivesÂ immunosuppression in the form of Campath as a prophylactic prior to the transplant and then must either receive Prograf, Cyclosporin, or Sirolimus (depending on the tissue transplanted) in order to suppress the patients immune system, allowing the graft to survive while avoiding graft-vs-host rejection. If we are going to talk about translational therapies, then let's get into the meat and stop chewing the fat.

If you read up about the other company conducting a human embryonic stem cell trial (Advanced Cell Tech) they are using terminally differentiated RPE cells derived from an embryonic stem cell line. They also have an extremely effective assay test that can identify any undifferentiated stem cells before they are injected. This should make any formation of teratomas Â nil. Regarding immunosuppression, they have minimized the need for this by operating in an immune privileged site (the eye). To deal with the moral issue, the company has a method of producing stem cells that does Â not destroy the embryo( single cell blastomere method)

To follow up on natboling1 comments, cell soting can be used to separate potentially harmful cells from hESCs. This can be acheived through labeling with a specific biomarker.

Commenting on the morass of citations that StemCellBlogger has previously listed, touting adult stem cells as the way to salvation, even with donor human hematopoietic stem cellsÂ (hHESCs) (adult stem cells), usedÂ in the treatment of leukemia patients,Â a patientÂ must undergo aÂ radiation treatment toÂ suppressÂ their immuneÂ systemÂ prior to receiving the donorÂ hHESCs. StemCellBlogger commented on the need for immunosuppression when using hESCs inÂ clinical translational therapy. Given that a patient must receive a near lethal dose of radiation, knocking out their immune systemÂ BEFORE receiving hHESCs from aÂ registered DONOR, flies in the face of reason when compared to the immunosuppression required for hESC infusion.Â A patient receivng either a liver, kidney, pancreas or dual kidney pancreas organ transplant receivesÂ immunosuppression in the form of Campath as a prophylactic prior to the transplant and then must either receive Prograf, Cyclosporin, or Sirolimus (depending on the tissue transplanted) in order to suppress the patients immune system, allowing the graft to survive while avoiding graft-vs-host rejection. If we are going to talk about translational therapies, then let's get into the meat and stop chewing the fat.

If you read up about the other company conducting a human embryonic stem cell trial (Advanced Cell Tech) they are using terminally differentiated RPE cells derived from an embryonic stem cell line. They also have an extremely effective assay test that can identify any undifferentiated stem cells before they are injected. This should make any formation of teratomas Â nil. Regarding immunosuppression, they have minimized the need for this by operating in an immune privileged site (the eye). To deal with the moral issue, the company has a method of producing stem cells that does Â not destroy the embryo( single cell blastomere method)

To follow up on natboling1 comments, cell soting can be used to separate potentially harmful cells from hESCs. This can be acheived through labeling with a specific biomarker.

Commenting on the morass of citations that StemCellBlogger has previously listed, touting adult stem cells as the way to salvation, even with donor human hematopoietic stem cellsÂ (hHESCs) (adult stem cells), usedÂ in the treatment of leukemia patients,Â a patientÂ must undergo aÂ radiation treatment toÂ suppressÂ their immuneÂ systemÂ prior to receiving the donorÂ hHESCs. StemCellBlogger commented on the need for immunosuppression when using hESCs inÂ clinical translational therapy. Given that a patient must receive a near lethal dose of radiation, knocking out their immune systemÂ BEFORE receiving hHESCs from aÂ registered DONOR, flies in the face of reason when compared to the immunosuppression required for hESC infusion.Â A patient receivng either a liver, kidney, pancreas or dual kidney pancreas organ transplant receivesÂ immunosuppression in the form of Campath as a prophylactic prior to the transplant and then must either receive Prograf, Cyclosporin, or Sirolimus (depending on the tissue transplanted) in order to suppress the patients immune system, allowing the graft to survive while avoiding graft-vs-host rejection. If we are going to talk about translational therapies, then let's get into the meat and stop chewing the fat.